Staphylococcus aureus: The Bug Behind the Itch in Atopic Dermatitis.

Pruritus or itch is a defining symptom of atopic dermatitis (AD). The origins of itch are complex, and it is considered both a defense mechanism and a cause of disease that leads to inflammation and psychological stress. Considerable progress has been made in understanding the processes that trigger itch, particularly the pruritoceptive origins that are generated in the skin. This perspective review discusses the implications of a recent observation that the V8 protease expressed by Staphylococcus aureus can directly trigger sensory neurons in the skin through activation of protease-activated receptor 1. This may be a key to understanding why itch is so common in AD because S. aureus commonly overgrows in this disease owing to deficient antimicrobial defense from both the epidermis and the cutaneous microbiome. Increased understanding of the role of microbes in AD provides increased opportunities for safely improving the treatment of this disorder.

Staphylococcus scratches its itch.

Itch exacerbates infection and inflammation-associated skin pathology. In this issue of Cell, Deng et al. identify a V8 protease released by Staphylococcus aureus triggering itch via neuronal protease-activated receptor 1. In so doing, they uncover profound consequences of microbial neurosensory modulation and the ensuing scratch-induced tissue damage that potentiates infection.

S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis.

Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrier is constantly exposed to microbes and their products. However, the role of microbes in itch generation is unknown. Here, we show that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch. Epicutaneous S. aureus exposure causes robust itch and scratch-induced damage. By testing multiple isogenic bacterial mutants for virulence factors, we identify the S. aureus serine protease V8 as a critical mediator in evoking spontaneous itch and alloknesis. V8 cleaves proteinase-activated receptor 1 (PAR1) on mouse and human sensory neurons. Targeting PAR1 through genetic deficiency, small interfering RNA (siRNA) knockdown, or pharmacological blockade decreases itch and skin damage caused by V8 and S. aureus exposure. Thus, we identify a mechanism of action for a pruritogenic bacterial factor and demonstrate the potential of inhibiting V8-PAR1 signaling to treat itch.

Cutaneous candidiasis caused by Candida kefyr.

Candidiasis is an acute or subacute fungal infection caused by fungi that belongs to candida genus, with Candida albicansbeing the most frequent causative agent. Candida kefyr is a rare cause of candidiasis which has been reported in systemic candidiasis and deep infections. However, to date, it has never been reported as a cause in dermatophytosis. We report a case of candidiasis caused by Candida kefyr in a 72-year-old woman with a chief complaint of pruritic erythematous rash on the back from one day prior to admission. Diagnosis was established based on clinical features, direct microscopic examination with 10% potassium hydroxide solution, gram staining. The fungal species was determined by carbohydrate fermentation test which showed a positive result for Candida kefyr. The patient was treated with miconazole cream and fusidic cream and showed significant clinical improvement.

Topical clotrimazole cream for the treatment of tinea cruris: A retrospective study.

This retrospective study assessed the efficacy and safety of 1% topical clotrimazole cream for the treatment of patients with tinea cruris (TC).We included 86 patients with confirmed TC for the presence of fungal hyphae. Of those, 43 patients received 1% topical clotrimazole cream for a total of 4 consecutive weeks, and were assigned to an experimental group. The other 43 patients underwent 1% topical butenafine cream for a total of 2 consecutive weeks, and were allocated to a control group. The efficacy and safety were measured and analyzed after 4 weeks treatment.After treatment, patients in both groups achieved better improvements in erythema (P < .01), scaling (P < .01), itching (P < .01), and KOH-negative results (P < .01), compared with those in patients before the treatment. However, there were not significant differences in erythema (P = .61), scaling (P = .57), itching (P = .47), and KOH-negative results (P = .67) between 2 groups. In addition, no treatment-related adverse events were recorded in both groups.Both 1% topical clotrimazole and butenafine cream are found to be effective and safe for patients with TC. However, there is not significant difference in efficacy and safety between two groups.

The Role of the Microbiome and Microbiome-Derived Metabolites in Atopic Dermatitis and Non-Histaminergic Itch.

Recent advances in our understanding of the pathophysiology of atopic dermatitis (AD) have revealed that skin microbiome dysbiosis plays an important role in the disease. In this review, we describe how changes in the structure and function of the microbiome are involved in the pathogenesis of AD. We highlight recent data showing that differential changes in microbial diversity, both within and across communities from different body habitats (including the skin, gut, and oral mucosa), are associated with the development and severity of AD. We also describe recent evidence demonstrating that the metabolic activity of the skin microbiome can act as a regulator of inflammation, with alterations in the level of a skin microbiome-derived tryptophan metabolite, indole-3-aldehyde (IAId), being shown to play a role in AD. The various mechanisms by which interactions between the microbiome and components of the non-histaminergic pathway result in itch in AD are also discussed.

Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo-Controlled, Phase II Trial.

Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (-18.5%; 95% confidence interval, -32.9 to -1.0; P = 0.04; and -8.2; 95% confidence interval, -16.3 to -0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials.

Impact of the early-life skin microbiota on the development of canine atopic dermatitis in a high-risk breed birth cohort.

Canine atopic dermatitis (CAD) is a prevalent inflammatory skin disease of dogs worldwide. Certain breeds such as the West Highland White Terriers (WHWT) are predisposed to suffer from CAD. Microbial dysbiosis is known to play a significant role in the pathogenesis of the disease, which is similar to its human counterpart, atopic dermatitis (AD). To date, no large cohort-study has been conducted in a predisposed dog breed to study the impact of the early-life microbiota on the development of CAD, as well as the possible implication of factors such as hygiene and access to the outdoors. In this study skin samples of 143 WHWT, including 109 puppies up to three weeks old and 34 parent dogs, from 17 breeders, were subjected to 16S rRNA gene and ITS2 amplicon sequencing to disclose the bacterial and fungal oral and skin microbiota, respectively. The oral samples served as a control group to confirm differences between haired and mucosal surfaces. The cutaneous microbiota differed between sample sites and age of the dogs. The season of sampling, geographical origin as well as hygiene status of the household and the access to the outdoors shaped the skin microbiota of the puppies significantly. However, we found that the individual early-life microbiota did not predispose for the later development of CAD.

Candidatus Mycoplasma haemohominis in Human, Japan.

Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance-determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.

Trichophyton mentagrophytes - a new genotype of zoophilic dermatophyte causes sexually transmitted infections.

BACKGROUND: A new genotype of the zoophilic fungal species Trichophyton (T.) mentagrophytes was recently described in two studies. It was isolated from three patients who had visited Southeast Asia and one patient who had visited Egypt. In contrast to these studies, we have observed a number of cases with the dimensions of an epidemic outbreak. PATIENTS AND METHODS: At the University Hospital Charité Berlin, 43 patients, mostly suffering from highly inflammatory, painful and persistent infections of the pubogenital region were observed between January 2016 and July 2017. Mycological examination was performed with fungal culture and sequencing of the ITS (internal transcribed spacer) region of the ribosomal DNA. Three additional genomic regions were spot-checked. RESULTS: In 37 of the cases, a new genotype of T. mentagrophytes (referred to here as T. mentagrophytes VII) was isolated as the etiological agent, and sequencing revealed identical sequences for all isolates. Most of the infected patients had no history of travel, and only two patients reported contact with animals. CONCLUSIONS: The new genotype clustered phylogenetically among the strains of the zoophilic species T. mentagrophytes with four different DNA markers. While human-to-human transmission of zoophilic dermatophytes is rare, transmission via sexual contact seemed to be quite effective here.

From Probiotic to Prebiotic Using Thermal Spring Water.

BACKGROUND: La Roche-Posay Thermal Spring Water (LRP-TSW) exhibits both probiotic and prebiotic properties enhancing the diversity of the skin microbiota. METHODS: A review was undertaken to explore the role of LRP-TSW as a topical probiotic and prebiotic therapy in improving the diversity of the skin microbiota and reducing dryness and pruritus in inflammatory skin diseases. RESULTS: The concentration of minerals and non-pathogenic microbes in LRP-TSW may explain its therapeutic benefit when used for inflammatory skin diseases. Clinical studies have shown that topical LRP-TSW treatment results in increases in Gram-negative bacteria with reduction of Gram-positive bacteria, and improvements in skin microbial diversity. At the same time skin condition in atopic dermatitis, psoriasis, and general dryness in otherwise healthy skin, has been shown to improve. CONCLUSIONS: Enhancement of skin microbiota diversity using topical LRP-TSW may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. J Drugs Dermatol. 2018;17(6):657-662.

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Glyoxal-induced exacerbation of pruritus and dermatitis is associated with staphylococcus aureus colonization in the skin of a rat model of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease associated with hyperreactivity to environmental triggers. Among those, outdoor air pollutants such as particulate matter (PM) have been reported to aggravate pre-existing AD. However, underlying mechanisms of air pollution-induced aggravation of AD have hardly been studied. OBJECTIVE: To investigate the molecular mechanisms by which glyoxal, a PM-forming organic compound, exacerbates the symptoms of AD induced by neonatal capsaicin treatment. METHODS: Naïve and AD rats had been exposed to either fresh air or vaporized glyoxal for 5 weeks (2 h/day and 5 days/week) since one week of age. Pruritus and dermatitis were measured every week. The skin and blood were collected and immunological traits such as Staphylococcus aureus skin colonization, production of antimicrobial peptides and immunoglobulin, and mRNA expression of inflammatory cytokines were analyzed. RESULTS: Exposure to glyoxal aggravated pruritus and dermatitis in AD rats, but did not induce any symptoms in naïve rats. Staphylococcus aureus skin colonization was increased in the skin of both naïve and AD rats. Expression of antimicrobial peptides such as LL-37 and ß-defensin-2 was also increased by exposure to glyoxal in the skin of both naïve and AD rats. The mRNA expression of Th1-related cytokines was elevated on exposure to glyoxal. However, serum immunoglobulin production was not significantly changed by exposure to glyoxal. CONCLUSION: In AD rats, exposure to glyoxal exacerbated pruritus and cutaneous inflammation, which was associated with increased colonization of S. aureus and subsequent immunological alterations in the skin.

Disfiguring facial lesions and loss of sensation.

Hansen disease (leprosy) continues to be prevalent in some regions of Africa, Asia, and South America, and each year 100 to 300 cases are reported in the United States, especially in immigrants and patients exposed to armadillos. Treatment depends on patient presentation. Hansen disease remains highly stigmatized, though it is now clear that it is not readily transmitted through casual physical contact.

Delta Hemolysin and Phenol-Soluble Modulins, but Not Alpha Hemolysin or Panton-Valentine Leukocidin, Induce Mast Cell Activation.

Mast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of human Staphylococcus aureus-infected skin abscess specimens, respectively, but they were produced in vitro by all clinical isolates. The results suggest that Hld and PSM-α1 produced in vivo during S. aureus skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of S. aureus via the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of S. aureus strains with a functional agr system.

Small animal disease surveillance: pruritus, and coagulase-positive staphylococci.

Presentation for pruritus comprised 6.5 per cent, 3.6 per cent and 2.0 per cent of canine, feline and rabbit consultations, respectively, between January 2014 and June 2016Topical antimicrobials were the most commonly prescribed pruritus treatments for dogs (33.6 per cent of consultations); for cats, it was systemic glucocorticoids (53.5 per cent)In surveillance of coagulase-positive staphylococci, 16 per cent of 176 coagulase-positive staphylococci isolated from canine diagnostic samples were sensitive to all tested antibacterial classes; multidrug resistance (resistance to three or more antibacterial classes) was found in 6.8 per cent.

Therapeutic effect of Castellani's paint in patients with an itchy ear canal.

OBJECTIVE: To examine the effects of Castellani's paint on symptomatic relief and skin flora in patients with an itchy external ear canal. METHODS: Subjective pruritus scores, and erythema and desquamation scores, were noted in 61 patients with an itchy external ear canal. External ear canal skin swabs were taken for bacterial and fungal cultures. Patients were then randomly divided into three groups: either Castellani's paint (group one) or steroid ear drops (group two) were instilled, or non-impacted cerumen was removed (group three). Patients were re-assessed at one month after the initial visit. RESULTS: After treatment, subjective pruritus scores were significantly lower in all groups, erythema scores were significantly decreased in group one, and desquamation scores were significantly reduced in groups one and two, when compared with pre-treatment scores. Reproduction density of bacteria including normal flora was decreased in group one. However, the types of bacteria that constitute the normal flora of the external ear canal were unchanged. CONCLUSION: Castellani's paint can be administered safely, effectively and easily, without affecting the type of external ear canal skin bacteria, in patients with an itchy external ear canal.

Pain and Itch: Beneficial or Harmful to Antimicrobial Defense?

Pain and itch are unpleasant sensations accompanying many microbial infections. Recent studies demonstrate that pain- and itch-mediating somatosensory neurons are able to directly detect pathogens, triggering neuronal activation and subsequent regulation of immune responses. We discuss whether pain and/or itch during infection is beneficial or harmful to host antimicrobial defense.